Downstream Processing: Purifying Complex Antibody Therapeutics When Target Molecules Misbehave

As antibody-based therapeutics move beyond IgG monoclonal antibodies, downstream process development teams have to purify molecules that do not always fit established platform assumptions. Bispecifics, multispecifics, antibody fragments, Fc-fusion proteins, ADCs, and other engineered formats can introduce new challenges in assembly, stability, impurity profiles, and scalability. Separation of the target molecule from mispaired chains, homodimers, aggregates, fragments, free light chains, persistent host cell proteins, and format-specific product variants can fall outside the limits of standard Protein A, AEX, and CEX purification workflows. For many PD teams, the platform process remains the proper starting point, but the molecule does not always behave like the platform expects.

In this GEN webinar, downstream process development and scale up manufacturing specialists will discuss practical strategies for building robust purification processes when the target molecule misbehaves. The discussion will explore how teams decide whether to stay with a platform, adapt it, or move to a more molecule-specific toolbox, how alternative affinity approaches can help when Protein A lacks selectivity or is not applicable, and how polishing strategies with IEX, HIC, and mixed-mode chromatography can be used to address difficult product- and process-related impurities. The panel will also discuss how to balance speed, yield, purity, cost of goods, analytical burden, scalability, and regulatory expectations from early development through tech transfer and manufacturing of standard mAbs and beyond.

A live Q&A session will follow the presentation offering you a chance to pose questions to our expert panelists.

Produced with support from: